4-119136010-C-T

Variant names:

• chr4-119136010-C-T
• rs7653944
• NM_016599.5:c.-15+28C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016599.5(MYOZ2):​c.-15+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 159,764 control chromosomes in the GnomAD database, including 79,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75775 hom., cov: 33)
  • Exomes 𝑓: 1.0 (3696 hom.)
• Consequence: MYOZ2 NM_016599.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65
• Publications: 2 publications found

Genes affected

MYOZ2 (HGNC:1330): (myozenin 2) The protein encoded by this gene belongs to a family of sarcomeric proteins that bind to calcineurin, a phosphatase involved in calcium-dependent signal transduction in diverse cell types. These family members tether calcineurin to alpha-actinin at the z-line of the sarcomere of cardiac and skeletal muscle cells, and thus they are important for calcineurin signaling. Mutations in this gene cause cardiomyopathy familial hypertrophic type 16, a hereditary heart disorder. [provided by RefSeq, Aug 2011]

MYOZ2 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy 16

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 4-119136010-C-T is Benign according to our data. Variant chr4-119136010-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016599.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ2	NM_016599.5	MANE Select	c.-15+28C>T		intron	N/A	NP_057683.1	Q9NPC6
	MYOZ2	NM_001440645.1		c.-15+28C>T		intron	N/A	NP_001427574.1
	MYOZ2	NM_001440646.1		c.-15+28C>T		intron	N/A	NP_001427575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ2	ENST00000307128.6	TSL:1 MANE Select	c.-15+28C>T		intron	N/A	ENSP00000306997.6	Q9NPC6
	MYOZ2	ENST00000958711.1		c.-15+28C>T		intron	N/A	ENSP00000628770.1
	MYOZ2	ENST00000890356.1		c.-15+24C>T		intron	N/A	ENSP00000560415.1

Frequencies

GnomAD3 genomes AF: 0.997 AC: 151841 AN: 152252 Hom.: 75716 Cov.: 33

Gnomad AFR AF: 0.991

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.996

GnomAD4 exome AF: 1.00 AC: 7393 AN: 7394 Hom.: 3696 Cov.: 0 AF XY: 1.00 AC XY: 3864 AN XY: 3864

African (AFR) AF: 1.00 AC: 30 AN: 30

American (AMR) AF: 0.999 AC: 1249 AN: 1250

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 68 AN: 68

East Asian (EAS) AF: 1.00 AC: 350 AN: 350

South Asian (SAS) AF: 1.00 AC: 714 AN: 714

European-Finnish (FIN) AF: 1.00 AC: 168 AN: 168

Middle Eastern (MID) AF: 1.00 AC: 12 AN: 12

European-Non Finnish (NFE) AF: 1.00 AC: 4474 AN: 4474

Other (OTH) AF: 1.00 AC: 328 AN: 328

GnomAD4 genome AF: 0.997 AC: 151959 AN: 152370 Hom.: 75775 Cov.: 33 AF XY: 0.998 AC XY: 74324 AN XY: 74510

African (AFR) AF: 0.991 AC: 41210 AN: 41576

American (AMR) AF: 0.998 AC: 15283 AN: 15314

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 1.00 AC: 4834 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68034 AN: 68040

Other (OTH) AF: 0.996 AC: 2106 AN: 2114

Alfa AF: 0.999 Hom.: 9234

Bravo AF: 0.997

Asia WGS AF: 0.999 AC: 3475 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		1.7
PromoterAI		0.036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7653944; hg19: chr4-120057165;